# Nevus associated microRNAs as mediators of BRAF-induced growth arrest and biomarkers of melanoma progression

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $341,867

## Abstract

Summary
A single driver mutation, BRAFV600E, drives half of all melanomas. However, in the majority of cases,
acquisition of BRAFV600E instead drives benign tumors, such as melanocytic nevi (the common mole). We seek
to decipher the intracellular mechanisms that prevent full transformation, and harness this knowledge to
develop candidate early diagnosis and chemoprevention strategies. We have discovered a signature of
microRNAs (miRNA) as the most differentially expressed transcripts distinguishing nevi from either normal
melanocytes or melanomas. We have reported that expression of these miRNAs classifies biopsied pigmented
neoplasms with high diagnostic accuracy. To determine whether knowledge of these miRNAs could aid in the
prevention of melanoma: First, we conducted a comprehensive identification and functional screen of the
targets of the most predictive miRNA, MIR211-5p. Using freshly isolated and CRISPR engineered human
normal, nevus and melanoma melanocytes, we identified inhibition of AURKB expression as a critical
mechanism driving both BRAFV600E and MIR211-5p associated growth arrest in vitro. Therefore, in Aim 1, our
objective is to assess the roll of the MIR211-5p/AURKB axis in nevus formation and transformation in vivo, and
the efficacy of disrupting this axis in melanoma chemoprevention. Second, we generated a non-invasive assay
for miRNA screening of pigmented lesions prior to biopsy. In a small pilot study, we found the high accuracy of
classification of melanocytic neoplasia was retained. In Aim 2, our objective is to validate the utility of using
non-invasive profiling of the miRNA signature to screen pigmented skin lesions.
Three advances distinguish our proposal. The first is the reproducibility of our miRNA classifier, currently
validated on six independent datasets. Second, our model systems for this disease—engineered primary
human melanocytes, nevi, and melanomas, combined with an in vivo system that recapitulates both the
genetics and progression of melanoma—puts us in a unique position to control for context-specific effects
when studying these critical events. Third, is our development of a non-invasive miRNA profiling assay, a
molecular profiling technique that is both non-invasive and lesion-specific. Our team, consisting of experts in
both the basic biology of miRNA and melanoma, in vivo models of melanoma, topical drug delivery, and the
daily practice of melanoma surveillance, allows us to comprehensively tackle this project.
This project has both basic and clinical potential significance. Our studies explore novel explanations for nevus
initiation, driven by observations made from clinical lesions. We expect these studies to directly result in an
increase in the early detection of melanomas and preclinical validation of a strategy for topical
chemoprevention for particularly high-risk individuals and/oror anatomic areas.

## Key facts

- **NIH application ID:** 10474476
- **Project number:** 5R01CA229896-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Robert Laird Judson-Torres
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $341,867
- **Award type:** 5
- **Project period:** 2021-08-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474476

## Citation

> US National Institutes of Health, RePORTER application 10474476, Nevus associated microRNAs as mediators of BRAF-induced growth arrest and biomarkers of melanoma progression (5R01CA229896-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10474476. Licensed CC0.

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